In the previous funding period, the Southern California Islet Cell Resources (SC-ICR) Center has established itself as one of the most productive islet transplantation centers in ICR program while also providing high quality islets to ICR-approved projects nationwide. We have also assembled a consortium of several transplant centers in Southern California and are working to train and qualify them as islet transplantation sites which will use the clinical-grade islets produced by the SC-ICR. In these and other ways, the SC-ICR has demonstrated that it functions as a true islet cell resource center. In the upcoming period we will extend this success to improving islet cell isolation, characterization, and storage. In Specific Aim 1, we plan to expand the capacity of the SC-ICR up to three folds by constructing a fully dedicated facility, adding another islet isolation team, and increasing organ procurement activities. In Specific Aim 2, we are targeting a few crucial areas for improvement in islet recovery and potency. We are investigating oxygen supplementation at specific points in the islet isolation procedure, inhibition of pro-apoptotic pathways, and supplementation of growth factors to maximize the islet yield from every organ. In Specific Aim 3 we establish an extensive platform of islet characterization assays based on latest technologies. These assays focus on providing validated characterization of islet identity and purity, quantitative functional assays for determining islet potency, and establishment of a multicenter study to identify molecules that are associated with clinical outcome. In Specific Aim 4 we address the problem of islet shortage by development methods for islet storage and establishment of a national islet repository. We are also looking beyond cadaveric islet isolation to development of new sources of insulin-producing cells. Finally, we take seriously the purpose of the ICR program to foster cooperation between leading islet isolation centers and have established several collaborative efforts with other members of the ICR program. As part of this effort, we are working to provide access to the many techniques, protocols, databases, and other bioinformatics resources created by the SC-ICR (Specific Aim 5). Thus, the SC-ICR program is positioned to lead advances in islet isolation and distribution activities and the development of technologies for improving islet yield, quality, quality assessment, and clinical utilization.